Doxorubicin-Loaded Mixed Micelles Using Degradable Graft and Diblock Copolymers to Enhance Anticancer Sensitivity.

In this study, a graft copolymer, poly(N-(2-hydroxypropyl) methacrylamide dilactate)-co-(N-(2-hydroxypropyl) methacrylamide-co-histidine)-graft-poly(d,l-lactide), and a diblock copolymer, methoxy poly(ethylene glycol)-b-poly(d,l-lactide), were assembled into a mixed micellar system to encapsulate the anticancer drug doxorubicin (Dox). This mixed micellar system possesses the hydrophobic lactide segment of both copolymers, which reinforces its stability in physiological milieus; the histidine molecules appended on the graft copolymer provide the desired pH-responsive behavior to release Dox during internalization in cancer cells. The results demonstrate that the two copolymers were successfully prepared, and their ratios in the mixed micelles were optimized on the basis of the results of the stability tests. Under acidic conditions, the mixed micelles swell and are able to release their payloads. Therefore, the in vitro results indicate that the Dox in the mixed micelles is released effectively in response to the environmental pH of the mimetic internalization process, increasing cancer cells' sensitivity toward Dox. The mixed micelles display low cytotoxicity due to the degradability of the polymers. The in vivo images show that the high stability of the mixed micelles ensures a high tumor accumulation. This selective tumor accumulation results in an excellent inhibition of in vivo tumor growth and a high rate of apoptosis in cancerous tissues, with low toxicity. This highly stable, mixed micellar system with a pH-dependent drug release, which enables the precise delivery of drugs to the tumor lesions, is feasible to employ clinically in cancer therapy.

Adsorption Behavior of High Stable Zr-Based MOFs for the Removal of Acid Organic Dye from Water.

Zirconium based metal organic frameworks (Zr-MOFs) have become popular in engineering studies due to their high mechanical stability, thermostability and chemical stability. In our work, by using a theoretical kinetic adsorption isotherm, we can exert MOFs to an acid dye adsorption process, experimentally exploring the adsorption of MOFs, their external behavior and internal mechanism. The results indicate their spontaneous and endothermic nature, and the maximum adsorption capacity of this material for acid orange 7 (AO7) could be up to 358 mg·g-1 at 318 K, estimated by the Langmuir isotherm model. This is ascribed to the presence of an open active metal site that significantly intensified the adsorption, by majorly increasing the interaction strength with the adsorbates. Additionally, the enhanced π delocalization and suitable pore size of UiO-66 gave rise to the highest host-guest interaction, which further improves both the adsorption capacity and separation selectivity at low concentrations. Furthermore, the stability of UiO-66 was actually verified for the first time, through comparing the structure of the samples before and after adsorption mainly by Powder X-ray diffraction and thermal gravimetric analysis.

Acquirement and disappearance of HBsAg and anti-HCV in an aged population: a follow-up study in an endemic township.

BACKGROUND: HBsAg and anti-hepatitis C virus (anti-HCV) are stable markers and widely used. The seroconversion and seroclearance of HBsAg and anti-HCV are important for disease control and prognosis of diseases. AIMS: To investigate acquirement and disappearance of HBsAg and anti-HCV in an endemic area. METHODS: Seven years after a community screening, 1002 of 2909 residents of Tzukuan Township were recruited. HBsAg, anti-HCV and alanine transaminase (ALT) were checked in all who participated and hepatitis B virus (HBV) DNA, anti-HBs, anti-HBc, HCV RNA, anti-HDV and upper abdominal ultrasonography were studied in different groups. RESULTS: There were 461 male and 541 female residents with a mean age of 66.7 ± 8.6 years. No new HBsAg carrier was noted and the HBsAg clearance rate was 1.58% per year. One of the 17 cases with HBsAg clearance had positive HBV DNA, three had ALT elevation, two had cirrhosis and seven had anti-HBs seroconversion. Quantitative of HBsAg and HBV DNA were concordant and 78.1% subjects had low levels of titration. Anti-HBc alone contributed to 32.1% and was prominent in old age and the anti-HCV-positive group. The anti-HCV seroconversion rate was only 0.74% per year and household transmission was the only risk factor. Only 37.5% of cases with anti-HCV seroconversion had HCV viraemia and the anti-HCV seroreversion rate was 0.63% per year. The anti-HDV seroconversion rate was 0.72% per year and no subject showed anti-HDV clearance. CONCLUSIONS: Much higher rates of HBsAg seroclearance, anti-HCV seroreversion and anti-HBc alone were noted in this endemic area and no subject showed anti-HDV clearance.

Hepatitis delta virus and GBV-C infection in two neighboring hepatitis B virus and hepatitis C virus-endemic villages in Taiwan.

BACKGROUND: Previous reports in Taiwan have shown that the hepatitis B virus (HBV)- and hepatitis C virus (HCV)-endemic areas are also endemic for hepatitis D virus (HDV), GBV-C and TT virus. This study aimed to elucidate the epidemiology of HDV and GBV-C infection in two neighboring HBV- and HCV-endemic villages, to deduce the epidemiological characteristics of multiple viral infections in communities. METHODS: A total of 74 adult residents of Wukwai (W) village and 95 adults residents of Haipu (H) village were studied. Laboratory tests for all subjects included alanine transaminase (ALT), hepatitis B surface antigen (HBsAg), anti-HCV, HCV RNA, genotype of HCV, GBV-C RNA, and anti-GBV-C E2. Anti- HDV was checked only in HBsAg-positive subjects. RESULTS: Subjects from W village were older than those from H village (61.7 +/- 11.8 vs 56.6 +/- 16.4 years, p = 0.02). The prevalence of ALT elevation (37.8% vs 15.8%, p = 0.006), anti-HCV (67.6% vs 34.7%, p < 0.0001), and GBV-C infection (39.2% vs 24.2%, p = 0.054), and the distribution of HCV genotype 1b (37.8% vs 70.4%, p = 0.01) were different in W and H villages, respectively. Among anti-HCV-positive subjects, HCV RNA-positive rates were 75.9% (63/83), and were higher for men (88.2%) than women (67.3%). Only one HBsAg-positive subject was positive for anti-HDV, and one anti-HCVnegative subject was positive for HCV RNA. In multivariate analyses, GBVC infection correlated with HCV infection or HCV endemicity, and HCV RNA was the only determining factor in ALT elevation. CONCLUSION: In HBV and HCV-endemic areas, GBV-C was more prevalent in areas with a higher prevalence of anti-HCV. Positive HCV-RNA, but not GBV-C infection, was associated with ALT elevation.